•Fatigue behavior of additively manufactured Ti-6Al-4V is studied.•Effects of surface roughness and surface area are investigated.•Supporting fractography, including crack growth analysis, is ...presented.•The effect of specimen diameter on the fatigue strength is discussed.
Additive manufacturing has become an increasingly popular advanced manufacturing technique, however, many questions concerning the reliability of parts fabricated by methods such as laser powder bed fusion must be addressed. In this research, the effect of surface roughness and size is investigated by designing various additively manufactured Ti-6Al-4V specimen geometries. These as-built specimens were designed to specifically determine the effect of surface area and part diameter on the fatigue behavior of specimens fabricated diagonally from the substrate. Results indicate that the fatigue behavior is more sensitive to part diameter than surface area. Parts with diameters of 4.90 mm or less showed higher surface roughness on the down-skin surface. This variation diminished, however, for specimens with diameters larger than 4.90 mm. Additionally, as part diameter decreased, the difference between the load-bearing and nominal stress amplitudes, caused by surface roughness, increased, resulting in significant scatter in the high cycle fatigue data.
Adaptive laboratory evolution experiments provide a controlled context in which the dynamics of selection and adaptation can be followed in real-time at the single-nucleotide level. And yet this ...precision introduces hundreds of degrees-of-freedom as genetic changes accrue in parallel lineages over generations. On short timescales, physiological constraints have been leveraged to provide a coarse-grained view of bacterial gene expression characterized by a small set of phenomenological parameters. Here, we ask whether this same framework, operating at a level between genotype and fitness, informs physiological changes that occur on evolutionary timescales. Using a strain adapted to growth in glucose minimal medium, we find that the proteome is substantially remodeled over 40 000 generations. The most striking change is an apparent increase in enzyme efficiency, particularly in the enzymes of lower-glycolysis. We propose that deletion of metabolic flux-sensing regulation early in the adaptation results in increased enzyme saturation and can account for the observed proteome remodeling.
The present study focused on evaluation of anodized oxides prepared in four mixed acid electrolytes with and without phosphoric acid as a function of forming voltage. Specifically the oxide surface ...characteristics, the mechanical integrity, and the bioactive performance were evaluated for a range of forming voltages in each electrolyte. Surface analyses showed phosphorus incorporation into the oxide layer started at localized areas after a threshold forming voltage, but became more uniform at higher voltages. Oxide crystallinity and thickness were retarded by the phosphoric acid levels present in the anodization electrolytes. Surface roughness was shown to be electrolyte dependent as a function of forming voltage, and in general was shown to increase with increasing voltage. Samples anodized up to a forming voltage of 144V did not show any oxide failure through shear strength testing with only epoxy delamination for three of the electrolytes. At 180V, the oxide layers showed failure or partial failure at approximately 30–35MPa, which is stronger than many values previously reported for anodized coatings in the literature. Additionally, oxide films prepared in phosphoric acid containing electrolytes showed greater bioactivity through enhanced apatite formation. These anodized coatings exhibiting enhanced bioactivity show promise for promoting faster osseointegration while providing better implant stability due to the superior coating adhesion strengths.
•Oxide crystallinity and thickness were retarded by increasing phosphoric acid.•The uniformity of phosphorus uptake was shown to be forming voltage dependent.•Bond strengths of the anodized layers were greater than others previously reported.•Phosphorus and anatase containing oxide films showed enhanced bioactivity.
A substantial portion of people with COVID-19 subsequently experience lasting symptoms including fatigue, shortness of breath, and neurological complaints such as cognitive dysfunction many months ...after acute infection. Emerging evidence suggests that this condition, commonly referred to as long COVID but also known as post-acute sequelae of SARS-CoV-2 infection (PASC) or post-COVID-19 condition, could become a significant global health burden.
While the number of studies investigating the post-COVID-19 condition is increasing, there is no agreement on how this new disease should be defined and diagnosed in clinical practice and what relevant outcomes to measure. There is an urgent need to optimise and standardise outcome measures for this important patient group both for clinical services and for research and to allow comparing and pooling of data.
A Core Outcome Set for post-COVID-19 condition should be developed in the shortest time frame possible, for improvement in data quality, harmonisation, and comparability between different geographical locations. We call for a global initiative, involving all relevant partners, including, but not limited to, healthcare professionals, researchers, methodologists, patients, and caregivers. We urge coordinated actions aiming to develop a Core Outcome Set (COS) for post-COVID-19 condition in both the adult and paediatric populations.
Mass spectrometry is an important method for analysis of modified nucleosides ubiquitously present in cellular RNAs, in particular for ribosomal and transfer RNAs that play crucial roles in mRNA ...translation and decoding. Furthermore, modifications have effect on the lifetimes of nucleic acids in plasma and cells and are consequently incorporated into RNA therapeutics. To provide an analytical tool for sequence characterization of modified RNAs, we developed Pytheas, an open-source software package for automated analysis of tandem MS data for RNA. The main features of Pytheas are flexible handling of isotope labeling and RNA modifications, with false discovery rate statistical validation based on sequence decoys. We demonstrate bottom-up mass spectrometry characterization of diverse RNA sequences, with broad applications in the biology of stable RNAs, and quality control of RNA therapeutics and mRNA vaccines.
To investigate the role of the pathogenic prion protein (PrP
Sc) in controlling susceptibility to foreign prions, two Syrian hamster (SHa) prion strains, Sc237 and DY, were transmitted to transgenic ...mice expressing chimeric SHa/mouse PrP genes, Tg(MH2M). First passage of SHa(Sc237) prions exhibited prolonged incubation times, diagnostic of a species barrier. PrP
Sc of the new MH2M(Sc237) strain possessed different structural properties from those of SHa(Sc237), as demonstrated by relative conformational stability measurements. This change was accompanied by a disease phenotype different from the SHa(Sc237) strain. Conversely, transmission of SHa(DY) prions to Tg(MH2M) mice showed no species barrier, and the MH2M(DY) strain retained the conformational and disease-specific properties of SHa(DY). These results suggest a causal relationship between species barriers, changes in PrP
Sc conformation, and the emergence of new prion strains.
Enzymatic De Novo Pyrimidine Nucleotide Synthesis Schultheisz, Heather L; Szymczyna, Blair R; Scott, Lincoln G ...
Journal of the American Chemical Society,
01/2011, Letnik:
133, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The use of stable isotope labeling has revolutionized NMR studies of nucleic acids, and there is a need for methods of incorporation of specific isotope labels to facilitate specific NMR experiments ...and applications. Enzymatic synthesis offers an efficient and flexible means to synthesize nucleoside triphosphates from a variety of commercially available specifically labeled precursors, permitting isotope labeling of RNAs prepared by in vitro transcription. Here, we recapitulate de novo pyrimidine biosynthesis in vitro, using recombinantly expressed enzymes to perform efficient single-pot syntheses of UTP and CTP that bear a variety of stable isotope labeling patterns. Filtered NMR experiments on 13C, 15N, 2H-labeled HIV-2 TAR RNA demonstrate the utility and value of this approach. This flexible enzymatic synthesis will make implementing detailed and informative RNA stable isotope labeling schemes substantially more cost-effective and efficient, providing advanced tools for the study of structure and dynamics of RNA molecules.
We report on the selective acceleration of carbon ions during the interaction of ultrashort, circularly polarized and contrast-enhanced laser pulses, at a peak intensity of 5.5 × 1020 W/cm2, with ...ultrathin carbon foils. Under optimized conditions, energies per nucleon of the bulk carbon ions reached significantly higher values than the energies of contaminant protons ( 33 MeV / nucleon vs 18 MeV), unlike what is typically observed in laser-foil acceleration experiments. Experimental data, and supporting simulations, emphasize different dominant acceleration mechanisms for the two ion species and highlight an (intensity dependent) optimum thickness for radiation pressure acceleration; it is suggested that the preceding laser energy reaching the target before the main pulse arrives plays a key role in a preferential acceleration of the heavier ion species.
There is increasing concern over the extent to which bovine spongiform encephalopathy (BSE) prions have been transmitted to humans, as a result of the rising number of variant Creutzfeldt-Jakob ...disease (vCJD) cases. Toward preventing new transmissions, diagnostic tests for prions in livestock have been developed using the conformation-dependent immunoassay (CDI), which simultaneously measures specific antibody binding to denatured and native forms of the prion protein (PrP). We employed high-affinity recombinant antibody fragments (recFab) reacting with residues 95-105 of bovine (Bo) PrP for detection and another recFab that recognizes residues 132-156 for capture in the CDI. We report that the CDI is capable of measuring the disease-causing PrP isoform (PrP(Sc)) in bovine brainstems with a sensitivity similar to that of end-point titrations in transgenic (Tg) mice expressing BoPrP. Prion titers were approximately 10(7) ID(50) units per gram of bovine brainstem when measured in Tg(BoPrP) mice, a figure approximately 10 times greater than that determined by bioassay in cattle and approximately 10,000x greater than in wild-type mice. We also report substantial differences in BoPrP(Sc) levels in different areas of the obex region, where neuropathology has been consistently observed in cattle with BSE. The CDI was able to discriminate between PrP(Sc) from BSE-infected cattle and Tg(BoPrP) mice as well as from chronic wasting disease (CWD)-infected deer and elk. Our findings argue that applying the CDI to livestock should considerably reduce human exposure to animal prions.
The morbidity and mortality of cryptococcal meningoencephalitis (CM) in previously healthy, HIV-negative individuals is increasingly recognized. We administered a healthcare associated quality of ...life (QOL) survey to the largest longitudinally followed cohort of these patients in the United States. We identified moderate or severe self-reported impairment in at least one QOL domain in 61% of subjects at least one year following diagnosis. Self-reported cognitive impairment was noted in 52% and sleep disturbance was noted in 55%. This is the first comprehensive study of cross-sectional long-term QOL in previously healthy patients following cryptococcal infection.
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